Ikemoto S, Thompson K S, Takahashi M, Itakura H, Lane M D, Ezaki O
Division of Clinical Nutrition, National Institute of Health and Nutrition, Tokyo, Japan.
Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3096-9. doi: 10.1073/pnas.92.8.3096.
High-fat intake leading to obesity contributes to the development of non-insulin-dependent diabetes mellitus (NIDDM, type 2). Similarly, mice fed a high-fat (safflower oil) diet develop defective glycemic control, hyperglycemia, and obesity. To assess the effect of a modest increase in the expression of GLUT4 (the insulin-responsive glucose transporter) on impaired glycemic control caused by fat feeding, transgenic mice harboring a GLUT4 minigene were fed a high-fat diet. Low-level tissue-specific (heart, skeletal muscle, and adipose tissue) expression of the GLUT4 minigene in transgenic mice prevented the impairment of glycemic control and accompanying hyperglycemia, but not obesity, caused by fat feeding. Thus, a small increase (< or = 2-fold) in the tissue level of GLUT4 prevents a primary symptom of the diabetic state in a mouse model, suggesting a possible target for intervention in the treatment of NIDDM.
高脂肪摄入导致肥胖，进而促使非胰岛素依赖型糖尿病（NIDDM，2型）的发展。同样，喂食高脂肪（红花油）饮食的小鼠会出现血糖控制缺陷、高血糖和肥胖。为了评估适度增加GLUT4（胰岛素反应性葡萄糖转运蛋白）的表达对高脂喂养引起的血糖控制受损的影响，给携带GLUT4小基因的转基因小鼠喂食高脂肪饮食。转基因小鼠中GLUT4小基因在心脏、骨骼肌和脂肪组织等低水平组织特异性表达可预防高脂喂养引起的血糖控制受损和随之而来的高血糖，但不能预防肥胖。因此，GLUT4组织水平的小幅升高（≤2倍）可预防小鼠模型中糖尿病状态的主要症状，这表明它可能是干预NIDDM治疗的一个潜在靶点。
